Quantitative measurement of cholesterol homeostasis in man requires analysis of dietary cholesterol intake, absorption, endogenous synthesis, catabolism, excretion and pool sizes. To quantitate these parameters by currently available procedures it is necessary to maintain patients in a metabolic ward under controlled conditions. In addition, existing procedures are extremely time-consuming for both the patient and the clinical investigator and thus are applicable to the study of the effect of dietary factors on cholesterol homeostasis in only a limited number of patients. The proposed research project is designed to develop modifications of existing procedures in order to apply them to the study of nutritional effects on cholesterol homeostasis in free-living outpatients. By application of stable isotope technology and validation of the proposed methods under metabolic ward conditions, techniques to measure each of the major determinants of cholesterol homeostasis in man will be applied to the study of: 1) the effect of fat quality and cholesterol quantity on variations in the feedback control of cholesterol metabolism; 2) the effect of long-term ingestion of polyunsaturated fat diet on the size of the body pools of cholesterol; and 3) the effect of early post-natal nutrition on cholesterol homeostasis in children. The project's ultimate goal is to develop and apply methods suitable for the identification of those members of the population who have precise or imprecise control of cholesterol homeostasis as affected by dietary factors, to determine the effectiveness of dietary control in reducing tissue cholesterol concentrations, and to define the effect of nutritional factors in cholesterol homeostasis. Analysis of individual patient responses to given dietary interventions would allow pathogenetic distintions to be made and indicate the most appropriate individual patient therapy on a rational basis.